This week I read an article in the newspaper about administering antipsychotics to teenagers at risk for schizophrenia. According to the article, the researchers conducted a experiment in which a group of teenagers was administered the atypical antipsychotic, olanzapine (Zyprexa). They had to terminate the study prematurely due to too many participants dropping out, presumably due to weight gain as a side-effect. I will try to show that their research design is flawed; and that it is simple to see why weight gain would coincide with the administration of olanzapine.
The study mistakenly assumes that we can diagnose schizophrenia in a "larval" state prior to a first psychotic episode. In reality, we there could be hundreds of thousands of causes for schizophrenia that we do not completely understand at this time. Assuming the researchers correctly identified participants with their study, there is still a problem with administering the drug to teenagers.
The young participants' nervous systems have not fully matured yet, so flooding their bodies with neuroleptics may harm the nascient systems developing in their brains. Given olanzapine's general affinity for many different receptor types, it could have widespread consequences detrimental to the "normal" development of the nervous system.
Particularly important is olanzapine's high affinity for dopaminergic receptors. Its main antipsychotic action is partly derived from its strong affinity for the D2 receptor. At the D2 receptor, olanzapine acts as an antagonist, decreasing normal activity for that neuron. In schizophrenic people, the current theory states that some of the symptoms may be generated by an excess of dopaminergic activity. So, decreasing dopamine levels should decrease expressed psychosis, theoretically. In practice, there are many other things going on.
My theory is that the weight-gain seen subsequent to administration of olanzapine is an inevitable homeostatic mechanism. The individual is trying to upregulate his or her levels of dopamine by eating. Dopamine is the main component of a "reward pathway" in our brain. This means that whenever we do something beneficial to our survival, that action is reinforced by a flood of dopaminergic activity in the brain. Eating, for instance is an evolutionarily beneficial behavior, which evokes a flood of dopamine. It could be the case that these teenagers are trying to bring their levels of dopamine back to their individual baselines by overeating.
So, not only is it a possibility that the researchers conducted their experiment on teenagers who never would have fully developed schizophrenia, but also their finding (althought it was not really an initial goal of the experiment) that olanzapine causes overeating as a side-effect (or main effect, if you ask me) is blatantly obvious, given the drug's receptor profile.